1. Field of the Invention
The present invention relates generally to the field of cancer. More specifically, the present invention relates to antigens specific for melanoma carcinomas.
2. Description of the Related Art
Several methods have been employed to isolate and clone tumor-associated antigens, and in general, these methods have relied upon the ability of the antigens to stimulate cytolytic T cells (1-4). These methods involve demanding techniques, including extensive manipulation and expansion of cytolytic T cells.
Furthermore, it is becoming increasingly apparent that tumor-bearing individuals also develop serological immune responses to tumor antigens. Antibodies directed towards mutated cellular genes have been described, including those reactive with mutant p53 (5, 6) and ras (7). In addition, humoral immune responses to non-mutated, aberrantly expressed tumor antigens, such as erbB-2 (8) and cathepsin D (9), have been reported.
The presence of humoral immunity to many known tumor-associated antigens suggests its use for identification of novel tumor-associated antigens. The feasibility of this strategy was demonstrated in a study by Pfreundschuh and coworkers (10, 11) who screened tumor-derived cDNA libraries with autologous patient sera and identified two known tumor antigens as well as several novel, putative tumor antigens. This technology, termed SEREX, for serological identification of antigens by recombinant expression cloning, has since been applied by many groups and has led to the substantial expansion of known tumor antigens (12).
Thus, the prior art is deficient in additional novel antigens specific to melanomas. The present invention fulfills this long-standing need and desire in the art.
Herein, the SEREX approach was used to identify melanoma antigens in patients undergoing active immunotherapy. The primary goal of identifying novel melanoma antigens is to expand the potential targets for immunotherapy. In addition, characterization of these proteins has the potential to impact on diverse areas of melanoma research including detection, diagnosis and staging, characterization of the genetic changes associated with tumorigenesis, and the principles of immune activation and tumor cell rejection.
Novel melanoma tumor-associated antigens may be useful for detection, diagnosis, and staging of melanomas. Novel melanoma tumor-associated antigens may also be useful for monitoring to detect recurrence and metastatic disease and to monitor disease burden (e.g., proteins expressed on the cell surface may provide targets for monitoring, i.e., via detection and imaging of tumors). Novel tumor-associated antigens may additionally be useful as targets for immunotherapy and intervention strategies.
One object of the present invention is to provide elanoma tumor-associated antigens and methods of using the elanoma tumor-associated antigens.
In one embodiment of the present invention, there is provided DNA encoding a melanoma tumor-associated antigen selected from the group consisting of: (a) isolated DNA as shown in SEQ ID Nos. 1-12; (b) isolated DNA which is complementary to isolated DNA of (a) above; and (c) isolated DNA differing from the isolated DNAs of (a) and (b) above in codon sequence due to the degeneracy of the genetic code.
In another embodiment of the present invention, there is provided an isolated and purified melanoma tumor-associated antigen coded for by the DNA disclosed herein.
In another embodiment of the present invention, there is provided a method for detecting mRNA coding for a melanoma tumor-associated antigen in a sample, comprising the steps of: (a) contacting a sample with an oligonucleotide probe having a sequence such as SEQ ID Nos. 1-12; and (b) detecting binding of the probe to the mRNA coding for a melanoma tumor-associated antigen in the sample.
In yet another embodiment of the present invention, there is provided a kit for detecting mRNA coding for a melanoma tumor-associated antigen, comprising: an oligonucleotide probe having a nucleotide sequence shown in SEQ ID Nos. 1-12. The kit may further comprises: a label with which to label the probe; and means for detecting the label.
In still yet another embodiment of the present invention, there is provided a method of detecting a melanoma tumor-associated antigen in a sample, comprising the steps of: (a) contacting a sample with an antibody specific for a melanoma tumor-associated antigen or a fragment thereof encoded by the DNA disclosed herein; and (b) detecting binding of the antibody to the melanoma tumor-associated antigen in the sample.
In another embodiment of the present invention, there is provided a kit for detecting a melanoma tumor-associated antigen, comprising: an antibody specific for a melanoma tumor-associated antigen or a fragment thereof encoded by the DNA disclosed herein. The kit may further comprise means to detect the antibody.
In another embodiment of the present invention, there is provided an antibody specific for a melanoma tumor-associated antigen or a fragment thereof encoded by the DNA disclosed herein.
In still yet another embodiment of the present invention, there is provided a method of screening for compounds that inhibit the activity of a melanoma tumor-associated antigen, comprising the steps of: (a) contacting a sample with a compound, wherein the sample comprises a melanoma tumor-associated antigen encoded by the DNA disclosed herein; and (b) assaying for activity of the melanoma tumor-associated antigen. Generally, a decrease in the melanoma tumor-associated antigen activity in the presence of the compound relative to the melanoma tumor-associated antigen activity in the absence of the compound is indicative of a compound that inhibits the activity of the melanoma tumor-associated antigen.
In another embodiment of the present invention, there is provided a method of inhibiting the growth of a melanoma tumor in an individual, comprising the steps of: (a) treating an individual with a therapeutic compound, wherein the therapeutic compound comprises a thereapeutic moiety and a targeting moiety, wherein the targeting moiety recognizes a melanoma tumor-associated antigen encoded by the DNA disclosed herein; wherein the therapeutic compound inhibits the growth of the melanoma tumor in the individual.
In another embodiment of the present invention, there is provided a cancer vaccine composition, comprising a vector capable of expressing a DNA molecule such as SEQ ID Nos. 1-12, and an appropriate adjuvant.
In another embodiment of the present invention, there is provided a method of vaccinating an individual against cancer, comprising the step of: (a) administering to the individual a vector capable of expressing a DNA molecule such as SEQ ID Nos. 1-12, wherein said expression elicits an immune response specific towards a melonoma-specific antigen, thereby inducing immune-mediated destruction of melanoma cells.
In another embodiment of the present invention, there is provided a method of inhibiting the growth of a melanoma tumor, comprising the steps of: (a) administering to an individual a cancer vaccine comprising a vector expressing a DNA such as SEQ ID Nos. 1-12, wherein administration of said vaccine induces an immune response, thereby inhibiting the growth of a melanoma tumor.
Other and further aspects, features, and advantages of the present invention will be apparent from the following description of the presently preferred embodiments of the invention. These embodiments are given for the purpose of disclosure.